1. Field of the Invention
The present invention relates to an animal suitable as a model for an allergic disorder. The present invention also relates to a method of screening agents for effectiveness in treating the allergic disorder using the inventive animal.
2. Description of the Background
Atopic dermatitis (AD) is known as one of the most common skin diseases among children with personal or a family history of atopy. Patients with AD frequently show elevated IgE levels against many allergens such as mites, pollens and grasses among others, and their prevalence is still increasing. AD is dependent upon not only genetic factors but also environmental factors as well. Epidemiological studies suggest that the onset of AD is influenced by environmental factors including mite antigens and air-pollution as well as mental stress. Mite antigens are especially of interest because of their high potency as allergens. For example, more than 90% patients with AD are positive for IgE-RAST for mite antigens.
Clinical symptoms of AD are improved when mites have been removed. In addition, immunological disturbances have been identified in patients with AD, such as overexpression of IL-4 and IL-5 in the affected skin. Defective IFN-γ production of T cells and IgE hyperproduction of B cells may result from hyperproduction of IL-4.
NC/Nga mice, originated from Japanese fancy mice (Nishiki mouse), were established as an inbred strain in 1955. The NC/Nga strain has some unusual biological characteristics: liver and kidney esterase like a DBA/2 strain, high susceptibility to X-irradiation, and high susceptibility to anaphylactic shock. Some researchers noticed development of spontaneous dermatitis just before or after weaning. For example, it has been shown that NC/Nga mice raised in air-uncontrolled conventional circumstances (conventional NC/Nga mice) spontaneously suffered from AD-like skin lesion with marked elevation in plasma level of total IgE, which was similar to human AD. In contrast, NC/Nga mice grown in a specific pathogen free environment (SPF NC/Nga mice) showed neither clinical sign nor IgE hyperproduction, suggesting the attribution of environmental factors to trigger the skin lesions.
Because multiple environmental factors may be involved in the AD-like inflammation of NC/Nga and because it takes 12–16 weeks for conventional NC/Nga mice to develop severe dermatitis, the conventional NC/Nga mice make it difficult and time consuming to analyze the pathogenesis and thus are not a suitable standard model of AD. Therefore, despite the fact that great attention has been paid to the pathogenesis of AD, the reason why NC/Nga mice suffer from such severe skin lesion only in the conventional conditions is not clearly understood.
Accordingly, it remains an important goal to establish a suitable animal model for more efficient elucidation of the AD pathogenesis, as well as other allergic disorders, and to develop new approaches for treating these disorders.